It has been demonstrated that CD8 positive cytotoxic T lymphocytes (CTLs) recognize epitope peptides derived from the tumor-associated antigens (TAAs) found on the major histocompatibility complex (MHC) class I molecule, and then kill the tumor cells. Since the discovery of the melanoma antigen (MAGE) family as the first example of TAAs, many other TAAs have been discovered, primarily through immunological approaches (NPL 1-2). Some of these TAAs are currently undergoing clinical development as immunotherapeutic targets.
Favorable TAAs are indispensable for the proliferation and survival of cancer cells. The use of such TAAs as targets for immunotherapy may minimize the well-described risk of immune escape of cancer cells attributable to deletion, mutation, or down-regulation of TAAs as a consequence of therapeutically driven immune selection. Accordingly, the identification of new TAAs capable of inducing potent and specific anti-tumor immune responses warrants further development and thus clinical application of peptide vaccination strategies for various types of cancer in ongoing (NPL 3-10). To date, there have been several reports of clinical trials using these TAAs-derived peptides. Unfortunately, only a low objective response rate has been observed in these cancer vaccine trials (NPL 11-13). Accordingly, there remains a need for new TAAs as immunotherapeutic targets.
UBE2T (ubiquitin-conjugating enzyme E2T: a typical amino acid sequence shown in SEQ ID NO: 65; a typical nucleotide sequence shown in SEQ ID NO: 64 (GenBank Accession No. NM_014176)) is one of the ubiquitin-conjugating enzymes (E2). UBE2T was reported to be one of the genes whose expression was up-regulated in human fibroblasts with serum stimulation (NPL 14). In the Fanconi anemia pathway, UBE2T binds FANCL, and is necessary for the DNA damage-induced monoubiquitination of FANCD2 (NPL 15-16). In recent studies, UBE2T was found to be frequently up-regulated in breast cancers, and interact and co-localize with the BRCA1/BRCA1-associated RING domain protein (BARD1) complex (PTL 1, NPL 17). Northern blot analysis in those studies revealed that UBE2T transcript was detected at very high level in breast cancer cell lines, but hardly detected in the vital organs. Furthermore, knockdowns of endogenous UBE2T by siRNA in cancer cell lines have been shown to significantly suppress growth of those cell lines (PTL 1-2, NPL 17).